Single nucleotide polymorphisms in GH-1
OwnerLinda Susan Wood, Susanne Wagner +1inventors
InventorsLinda Susan Wood, Susanne Wagner, Luis A. Parodi
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Abstract
The invention provides nucleic acid segments of the GH-1 gene including polymorphic sites. Allele specific primers and probes hybridizing to regions flanking these sites are also provided. The invention also provides methods for diagnosing GH-1 dysfunction.
Claims48
An isolated GH-1 diagnostic polynucleotide or its complement comprising between 10 and 800 contiguous nucleotides.
The isolated GH-1 diagnostic polynucleotide of claim which is derived from messenger RNA.
A polynucleotide for use in amplifying a segment of SEQ ID NO:4 comprising a polymorphic site.
A single-stranded DNA probe that hybridizes to a variant GH-1 gene and not to a wild type GH-1 gene, wherein the variant GH-1 gene is selected from the group consisting of:
- SEQ ID NO:4 having a “C” at position 1665,
- SEQ ID NO:4 having a “T” at position 1973,
- SEQ ID NO:4 having a “T” at position 2034,
- SEQ ID NO:4 having a “A” at position 2069,
- SEQ ID NO:4 having a “A” at position 2070,
- SEQ ID NO:4 having a “T” at position 2081,
- SEQ ID NO:4 having a “C” at position 2345
- SEQ ID NO:4 having a “G” at position 2533
- SEQ ID NO:4 having a “G” at position 3007
A method for classifying a nucleic acid molecule encoding GH-1 or a fragment thereof obtained from an individual for diagnostic or prognostic purposes, comprising;
- determining the identity of a nucleotide from said nucleic acid which corresponds to the nucleotide occupying at least one GH-1 polymorphic site selected from the group consisting of:
- S1, S2, S3, S4, S5, S6, S7, S8 and S9 on either the coding or non-coding strand.
A method of evaluating therapy with an agent acting on GH-1 dysfunction for treatment of a patient, comprising:
- (a) determining the identity of a nucleotide from a nucleic acid obtained from said patient which corresponds to the nucleotide occupying at least one GH-1 polymorphic site on either the coding or non-coding strand;
- (b) evaluating whether said patient should undergo therapy with said agent.
A method of administering human growth hormone comprising administering human growth hormone to a patient previously determined to have a nucleotide at a GH-1 polymorphic site indicating GH-1 dysfunction wherein the previous determination has ascertained that any of the following conditions exist:
- (a) the identity of the nucleotide at S1 on the coding strand is C or G on the non-coding strand
- (b) the identity of the nucleotide at S2 on the coding strand is T or A on the non-coding strand
- (c) the identity of the nucleotide at S3 on the coding strand is T or A on the non-coding strand
- (d) the identity of the nucleotide at S4 on the coding strand is A or T on the non-coding strand
- (e) the identity of the nucleotide at S5 on the coding strand is A or T on the non-coding strand
- (f) the identity of the nucleotide at S6 on the coding strand is T or A on the non-coding strand
- (g) the identity of the nucleotide at S7 on the coding strand is C or G on the non-coding strand
- (h) the identity of the nucleotide at S8 on the coding strand is G or C on the non-coding strand
- (i) the identity of the nucleotide at S9 on the coding strand is C or G on the non-coding strand.
A method of selecting a therapy for a patient comprising,
- (a) determining the identity of a nucleotide which corresponds to the nucleotide occupying at least one GH-1 polymorphic site selected from the group consisting of:
- S1, S2, S3, S4, S5, S6, S7, S8 and S9. on either the coding or non-coding strand;
- (b) transmitting a descriptor of therapy selected based on the identity of the nucleotide at said GH-1 polymorphic site.
A method of haplotype determination in an individual for diagnostic or prognostic purposes, comprising
- determining a nucleotide on a single chromosome. which corresponds to the nucleotide occupying one or more GH-1 polymorphic sites selected from the group consisting of:
- S1, S2, S3, S4, S5, S6, S7, S8 and S9.
A diagnostic kit comprising the required components for the determination of the of the identity of the nucleotide or nucleotides occupying a GH-1 polymorphic site selected from the group consisting of:
- S1, S2, S3, S4, S5, S6, S7, S8 and S9 in small volumes in a self contained kit.
An antibody selected from the group of antibodies consisting of:
- (a) an antibody to an epitope comprising amino acid position 3 of SEQ ID NO:2 capable of distinguishing a threonine from an alanine at that amino acid position;
- or
- (b) an antibody to an epitope comprising amino acid position 19 of SEQ ID NO:
- 2 capable of distinguishing a proline from a serine at that amino acid position;
- (c) an antibody to an epitope comprising amino acid position 13 of SEQ ID NO:
- 3 capable of distinguishing an alanine from a valine at that amino acid position;
- (d) an antibody to an epitope comprising amino acid position 25 of SEQ ID NO:
- 3 capable of distinguishing phenylalanine from isoleucine or tyrosine at that amino acid position;
- (e) an antibody to an epitope comprising amino acid position 28 of SEQ ID NO:
- 3 capable of identifying a terminal tyrosine at that amino acid position;
- (f) an antibody to an epitope comprising amino acid position 47 of SEQ ID NO:
- 3 capable of distinguishing an asparagine from threonine at that amino acid position;
- (g) an antibody to an epitope comprising amino acid position 79 of SEQ ID NO:3 capable of distinguishing a serine from a cysteine at that amino acid position.
- (h) an antibody to an epitope comprising amino acid position 153 of SEQ ID NO:3 capable of distinguishing an aspartic acid from histidine at that amino acid position.
A isolated GH-1 mutant polypeptide comprising one or more of the following mutations:
- (a) the amino acid encoded by the GH-1 polymorphic site S3 is a valine
- (b) the amino acid encoded by the GH-1 polymorphic site S4 is a isoleucine
- (c) the amino acid encoded by the GH-1 polymorphic site S5 is a tyrosine
- (d) the amino acid encoded by the GH-1 polymorphic site S7 is a threonine
- (e) the amino acid encoded by the GH-1 polymorphic site S8 is a cysteine
- (f) the amino acid encoded by the GH-1 polymorphic site S9 is a histidine
A method for treating a disease state comprising the step of administering to a patient in need of such treatment an amount of a GH-1 mutant polypeptide sufficient to alter GH-1 activity in the tissues of said patient.
A method for classifying a GH-1 polypeptide obtained from an individual for diagnostic or prognostic purposes, to determine whether said polypeptide is a GH-1 mutant polypeptide comprising;
- determining the identity of an amino acid encoded by at least one GH-1 polymorphic site selected from the group consisting of:
- S1, S2, S3, S4, S5, S6, S7, S8 and S9.
A method of evaluating therapy with an agent acting on GH-1 dysfunction for treatment of a patient, comprising:
- (a) determining whether a GH-i polypeptide obtained from said patient is a GH-1 mutant polypeptide;
- (b) evaluating whether the patient should undergo therapy with said agent.
A method of administering human growth hormone comprising administering human growth hormone to a patient previously determined to express a mutant GH-1 polypeptide wherein the previous determination has ascertained that any of the following conditions exist:
- (a) the identity of the amino acid encoded by the GH-1 polymorphic site S1 is an alanine
- (b) the identity of the amino acid encoded by the GH-1 polymorphic site S2 is a serine
- (c) the identity of the amino acid encoded by the GH-1 polymorphic site S3 is a valine
- (d) the identity of the amino acid encoded by the GH-1 polymorphic site S4 is a isoleucine
- (e) the identity of the amino acid encoded by the GH-1 polymorphic site S5 is a tyrosine
- (f) the identity of the amino acid adjacent to the the GH-1 polymorphic site S6 is a terminal tyrosine
- (g) the identity of the amino acid encoded by the GH-1 polymorphic site S7 is a threonine
- (h) the identity of the amino acid encoded by the GH-1 polymorphic site S8 is a cysteine
- (i) the identity of the amino acid encoded by the GH-1 polymorphic site S9 is a histidine
A method of selecting a therapy for a patient comprising,
- (a) determining whether a GH-1 polypeptide obtained from said patient is a GH-1 mutant polypeptide
- (b) transmitting a descriptor of therapy selected based on the identity of an amino acid encoded by a GH-1 polymorphic site.
Dependencies are inferred from the claim text.